tbuckley/cabot-search huggingface dataset:
Abstract 296: Relationship Between Emergency Medical Service Response Time And Bystander Cardiopulmonary Resuscitation In Children With Out-of-hospital Cardiac Arrest: A Nationwide, Population-based Observational Study
Authors: Akira Funada, Yoshikazu Goto
Journal: Circulation (2022)

Introduction: Bystander cardiopulmonary resuscitation (CPR) and a short response time for emergency medical services (EMSs) are important determinants of survival after out-of-hospital cardiac arrest (OHCA). As asphyxia cardiac arrest is more common than cardiac arrest from a primary cardiac event in children, effective ventilation is vital during pediatric OHCA. Hypothesis: There would be no difference in post-pediatric OHCA between standard bystander CPR (S-CPR) with rescue breaths and chest-compression-only bystander CPR (CC-CPR) before EMS arrival if EMS response time is extremely short. Methods: The study included 13,719 Japanese children (aged &lt;18 years) from an All Japan Utstein-style registry who received bystander CPR post-OHCA between 2005 and 2019. Patients were divided into two groups: S-CPR (n = 5,369) and CC-CPR (n = 8,350). After propensity score matching, we compared the outcomes between the groups according to EMS response time. EMS response times were categorized into 13 groups: ≤2, 3-4, 5-6, 7-8, 9-10, 11-12, 13-14, 15-16, 17-18, 19-20, 21-22, 23-24, and ≥25 min. The primary study endpoint was 1-month neurologically intact survival, defined as a cerebral performance category score of 1 or 2 (CPC 1-2). Results: Propensity score matching was achieved for 4,639 of 5,369 patients with S-CPR (86,4%) and 4,639 of 8,350 patients with CC-CPR (55.6%). Overall 1-month CPC 1-2 rate in S-CPR was significantly higher than that of CC-CPR: 17.0% (788/4,639) vs. 9.3% (429/4,639, P &lt;0.0001). There were no significant differences in 1-month CPC 1-2 rate between S-CPR and CC-CPR groups when EMS response times were ≤2 min ( P = 0.17), 17-18 min ( P = 0.55), 19-20 min ( P = 0.14), 21-22 min ( P = 0.23), 23-24 min ( P = 1.00), and ≥25 min ( P = 0.07). However, the rate of 1-month CPC 1-2 was significantly higher with S-CPR than with CC-CPR when the EMS response time ranged 3-4 min ( P &lt; 0.01) to 15-16 min ( P &lt; 0.01). Conclusions: CC-CPR for children with OHCA before EMS arrival had a similar association with S-CPR for 1-month neurologically intact survival when EMS response time was ≤2 min and ≥17 min onward. However, 1-month neurologically intact survival in S-CPR was superior to CC-CPR when EMS response time was outside this range.
Abstract 9376: TRPM77 Knockdown Prevents Hypomagnesemia-Induced Oxidative Stress and Cardiac Diastolic Dysfunction
Authors: Man Liu, Hong Liu, Gyeoung-Jin Kang, Feng Feng, Samuel C Dudley
Journal: Circulation (2022)

Introduction: Our previous study has shown that 6-week low-Mg diet-induced hypomagnesemia results in mitochondrial dysfunction, cardiac diastolic dysfunction, and seizure-related death. Transient receptor potential cation channel subfamily M 7 (TRPM7) is a Mg transporter with both channel and kinase function located in the plasma membrane. We investigated the role of TRPM7 in hypomagnesemia-associated changes. Methods: For cardiac-specific knockdown of TRPM7, pAAV[miR30]-cTnT&gt;EGFP:Scramble-shRNA as control (Con) and pAAV[miR30]-cTnT&gt;EGFP:TRPM7 shRNA as TRPM7 knockdown (T7KD) were injected into mice through the jugular vein at 10 weeks old. One week later, mice were fed with a normal diet (nlMg, 2000 mg/kg Mg) or a low-Mg diet (HypoMg, 15-30 mg/kg Mg) for 4 weeks. Results: TRPM7 was increased significantly in wild type mouse hearts under the low-Mg diet (1.45±0.18-fold of mice with normal diet, P&lt;0.01). We therefore knocked down TRPM7 in the mouse heart to see if HypoMg-induced changes could be prevented. After 4 weeks of low-Mg diet, both Con and T7KD mice had hypomagnesemia with significantly decreased serum Mg levels (0.37±0.03 and 0.45±0.10 mM, respectively, vs 1.05±0.04 mM of Con-nlMg). All T7KD mice showed significantly decreased TRPM7 protein levels in the heart tissue (&lt;30% of Con-nlMg, P&lt;0.01). Cardiac diastolic dysfunction (E/e’) was prevented in T7KD-HypoMg mice (E/e’=16.2±1.9 vs. 20.7±1.5 of Con-HypoMg). Increased total protein oxidation (measured with nitro-tyrosine immunoprecipitation) in Con-HypoMg heart tissue (1.61±0.09-fold increase, P=0.045 vs. Con-nlMg) was normalized in the T7KD-HypoMg group (1.18±0.09-fold of Con-nlMg, P=0.45 vs. Con-nlMg). Conclusions: TRPM7 was upregulated in hypomagnesemia in hearts and its knockdown prevented hypomagnesemia-induced cardiac diastolic dysfunction and increased oxidative stress.
Abstract 9414: Machine Learning of Pressure-Strain Curve Analysis on Ultrasound Echocardiography Can Predict Cardiac Prognosis in Patients With Congestive Heart Failure
Authors: Masato Shimizu, Tomoko Manno, Takahiro Tsunoda, Hiroko Miyazaki, Yoshiki Misu, Tateishi Ryo, Masao Yamaguchi, Yosuke Yamakami, Nobutaka Kato, Hiroshi Shimada, Ami Isshiki, Shigeki Kimura, Hiroyuki Fujii, Makoto Suzuki, Mitsuhiro Nishizaki, Tetsuo Sasano
Journal: Circulation (2022)

Introduction: Machine learning (ML) of ultrasound echocardiography (UCG) has been developed, but the diagnostic performance of pressure-strain curve analysis by ML for cardiac prognosis in patients with congestive heart failure (CHF) was not studied. Hypothesis: ML of pressure-Strain curve analysis on UCG can predict cardiac prognosis in patients with CHF. Methods: We enrolled consecutive 141 sinus-rhythm patients who admitted for CHF (76.4±13.2years, 85men), in whom UCG was performed after initial treatment. Major adverse cardiac event (MACE) was defined as cardiac death during observation period and re-admission due to CHF. Eleven ML predictive models were constructed by PyCaret, compared their accuracy, and important predictors were evaluated by Shapley Additive exPlanations (SHAP) method. Results: Forty-five patients showed MACE (observation period: median 284 days). Ten significant predictors were extracted by logistic regression analysis. Mean of accuracy in 11 models were 0.712. Random Forest Classifier showed the highest accuracy (0.766). Diastolic blood pressure, E wave, and global positive work (derived from pressure-strain curve analysis) played essential role in the model. Conclusion: ML of pressure-strain curve analysis had powerful diagnostic performance for predicting cardiac prognosis of CHF patients.
Abstract 9582: Septin-4 Induces Cardiac Fibrosis After Pressure Overload
Authors: Dogacan Yucel
Journal: Circulation (2022)

Introduction: Under cardiac stress, the mammalian heart undergoes ventricular remodeling to maintain cardiac function. Although these remodeling changes are viewed as beneficial at first, they eventually lead to pathological fibrosis and apoptosis. The role of the small GTPase Septin-4 (Sept4) in regulating apoptosis and regeneration through survival of stem cells has been established in several organs. However, the role of Sept4 in the heart, an organ without stem cells, and a potential role in regulating the cardiac stress response is currently unknown. Hypothesis: Sept4 induces fibrosis and apoptosis in the mammalian heart after injury. Methods: 10-week-old Sept4 knockout (KO) and wild type (WT) mice underwent transverse aortic constriction injury (TAC). Functional and molecular analyses on KO and WT hearts were done either at baseline, 1- or 4-weeks post-injury timepoints depending on the assay. Results: Cardiac function was comparable between KO and WT mice under homeostatic conditions. After TAC injury, ejection fraction and fractional shortening were decreased significantly in WT mice but maintained in KO mice. The level of cardiomyocyte apoptosis was lower in KO hearts after injury with reduced development of fibrosis compared with WT hearts. We performed transcriptomic and proteomic analyses showing that KO hearts exhibited reduced levels of ECM deposition under both baseline and post-injury conditions. Furthermore, KO hearts were more compliant and demonstrated enhanced diastolic function compared to WT hearts. Mechanistically, Sept4 deletion blunted TGF-B signaling and Postn expression in cardiac fibroblasts after injury. In cultured cardiac fibroblasts, both Sept4 knockout and knockdown significantly decreased fibroblast activation after TGF-B treatment. Conclusions: We identified Sept4 as a crucial regulator of ECM remodeling in the heart. Sept4 deletion leads to reduced levels of cardiac fibrosis and alleviation of pressure overload-induced cardiac dysfunction. Overall, our study highlights Sept4 as a potential target to prevent pathological fibrosis in the heart.
Abstract 9496: Association Between Oral Anticoagulant Type and Hospital Readmission Rates Following Myocardial Infarction With Percutaneous Coronary Intervention in Patients With Nonvalvular Atrial Fibrillation
Authors: Nihar Desai, Afraim Botros, Ankita Panda, Qian Xia, Keith Huff
Journal: Circulation (2022)

Introduction: Clinical trials have shown improved outcomes with direct-acting oral anticoagulant (DOAC)- vs. warfarin-based regimens in patients with atrial fibrillation (AF) with acute coronary syndrome and/or undergoing percutaneous coronary intervention (PCI). This study investigated the impact of anticoagulant type on hospital readmission rates following a myocardial infarction (MI) managed with PCI in patients with nonvalvular AF (NVAF) in the real world. Methods: This was a retrospective, observational study using data from two US claims databases, Optum ® Research and PharMetrics ® Plus. Patients with NVAF who were hospitalized for MI, underwent PCI between January 1, 2014 and December 31, 2020, and initiated treatment with warfarin or a DOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) exclusively during the index hospitalization or ≤365 days after discharge were included. Once identified, patients were followed for up to 12 months post-discharge. Hospital readmission rates at 30, 90, 180, and 365 days were compared for DOACs vs warfarin using multivariate Cox proportional hazards modeling. Results: The Optum cohort included 2647 patients (1997 DOAC, 650 warfarin) and the PharMetrics cohort included 2056 (1468 DOAC, 588 warfarin). In both cohorts, unadjusted all-cause, stroke/systemic embolism (SE)-related, and bleed-related hospital readmission rates were lower for DOACs vs warfarin at all timepoints. Regression analysis showed a significantly lower risk of hospital readmission with DOACs vs warfarin ( Table ). Conclusions: Real-world data from two large claims databases demonstrated that post-hospitalization DOAC treatment was associated with lower hospital readmission rates than warfarin treatment in patients with NVAF who were hospitalized for MI and underwent PCI. These results thus demonstrate the value of DOAC treatment for these patients.
Abstract 9385: Adipokines and Venous Thromboembolism: The Multi- Ethnic Study of Atherosclerosis (MESA)
Authors: Eric K Broni, Oluseye Ogunmoroti, Renato Quispe, Ty Sweeney, Bhavya Varma, Oluwaseun E Fashanu, Pamela L Lutsey, Matthew A Allison, Moyses Szklo, Chiadi E Ndumele, Erin D Michos
Journal: Circulation (2022)

Introduction: Obesity leads to adipocyte hypertrophy and adipokine dysregulation, with implications for cardiovascular disease. Prior studies have linked adipokines to many obesity-related pathologies, with higher adiponectin levels considered cardioprotective whereas higher leptin and resistin are generally considered deleterious to cardiovascular health. In this regard, obesity is an independent risk factor for incident venous thromboembolism [VTE (deep vein thrombosis or pulmonary embolus)]. However, the associations of adipokines with VTE are not well established. Methods: We studied 1,888 MESA participants who were initially free of VTE and had adipokine levels measured at either visit 2 or 3. VTE was ascertained through hospitalization records and death certificates using ICD-9 and 10 codes. We used multivariable Cox proportional hazards regression to assess the association between 1 standard deviation (SD) log-transformed increments in adipokines and incident VTE. Results: The mean ± SD age was 64.7 ± 9.6 years; 50% women, 40% White, 20% Black, 26% Hispanic, and 13% Chinese - American participants. Median (IQR) of adiponectin, leptin and resistin were 17.3 (11.8 - 26.2) mcg/mL ,13.5 (5.6 - 28.2) ng/mL, and 15.0 (11.9 - 19.0) ng/mL respectively. There were 78 incident cases of VTE after a median of 9.7 (5.0 - 12.4) years of follow-up. The adjusted hazard ratio (95%) per 1 SD increment of adiponectin, leptin and resistin were 1.10 (0.86 - 1.42), 1.30 (0.97 - 1.74) and 1.39 (1.10 - 1.75), respectively (Table 1, Model 1 ). Associations for resistin persisted after adjustment for body mass index (Model 2) and computed tomography derived total visceral and subcutaneous adipose tissue area (Model 3). Conclusions: In this multi-ethnic cohort of adults free of cardiovascular disease at baseline, higher resistin levels were independently associated with greater risk of incident VTE. Larger prospective cohort studies are warranted to confirm this association.
Abstract 9251: Associations Between Ultra- or Minimally-Processed Food Intake and Three Adiposity Indicators Among US Adults: Nhanes 2011-16
Authors: Zefeng Zhang, Henry S Kahn, Sandra Jackson, Euridice Martinez, Cathleen Gillespie, Quanhe Yang
Journal: Circulation (2022)

Objectives: Ultra-processed food (UPF) intake is associated with BMI, but effects on regional adipose depots or related to minimally-processed food (MPF) intake are unknown. We examined associations between calories consumed (%kcal) from UPF or MPF and three adiposity indicators: supine sagittal abdominal diameter/height ratio (SADHtR, estimates visceral adiposity), waist circumference/height ratio (WHtR, estimates abdominal adiposity), and BMI. Methods: Cross-sectional data came from 12 297 adults aged ≥20 years in the National Health and Nutrition Examination Survey 2011-2016. NOVA classification identified UPF and MPF dietary items using 24-hr dietary recall, and usual %kcal from UPF and MPF were estimated by National Cancer Institute methods. Each adiposity indicator was scaled to its sex-specific tertile distribution. We evaluated the associations between %kcal from UPFs and MPFs and each adiposity indicator using multivariable linear and multinomial logistic regression models. Results: The multivariable-adjusted, standardized β-coefficients per 10% increase in UPF intake were 0.0926, 0.0846, and 0.0791 for SADHtR, WHtR, and BMI respectively (all P&lt;0.001; P&gt;0.26 for pairwise differences). For MPF intake the β-coefficients were -0.0901, -0.0806 and -0.0688 (all P&lt;0.001; P&gt;0.18 for pairwise differences). The adjusted odds ratios (95% CI) for adiposity tertile 3 vs . tertile 1 (comparing UPF intake quartiles 2, 3 and 4 to quartile 1) were 1.33 (1.22-1.45), 1.67 (1.43-1.95), and 2.24 (1.76-2.86), respectively, for SADHtR; 1.31 (1.19-1.44), 1.62 (1.37-1.91), and 2.13 (1.63-2.78) for WHtR; and 1.27 (1.16-1.39), 1.53 (1.31-1.79), and 1.96 (1.53-2.51) for BMI. MPF intake showed inverse associations with all three adiposity indicators with similar trends in association strength. Neither UPF nor MPF models had interactions by sex or age groups. Conclusions: Among US adults, the indicators of abdominal and visceral adiposity were positively associated with UPF intake and inversely associated with MPF intake. These findings support public programs to discourage consumption of UPFs and to encourage MPF consumption.
Abstract 9311: Disparities in Resource Utilization by Families of Children With Complex Cardiac Conditions
Authors: Francisca L Chou, Denis J Donovan, Rachel J Weller, Michael Fremed, julie S Glickstein, Usha S Krishnan
Journal: Circulation (2022)

Introduction: There are limited data documenting the various sources of medical information that families use to learn about complex pediatric cardiac conditions. Our study aims to characterize the types of resources families use to learn about complex cardiac conditions and to identify disparities in the use of these resources. Hypothesis: We hypothesize that there are significant variations in the types of resources utilized by families from different educational and socioeconomic backgrounds. Methods: A survey evaluating resources families use to better understand complex cardiac conditions was administered to caretakers and pediatric patients at Morgan Stanley Children’s Hospital. Pediatric patients with prior diagnoses of congenital heart disease, cardiac arrhythmia, and/or heart failure were included. Caretakers’ levels of education (less than 16 years vs. 16 years or more) and patients’ medical insurance types (public vs. private) were compared to the utilization of resources. Results: Surveys completed by 137 caretakers and 27 pediatric patients were analyzed. Websites were utilized by 72% of caretakers and 56% of pediatric patients. A significantly higher percentage of responders with private insurance and higher education reported using websites, healthcare professionals, and their personal network to learn about pediatric cardiac lesions (by insurance p=0.009, p=0.001, p=0.006; by education p=0.022, p&lt;0.001, p=0.018). A significantly larger percentage of responders with private medical insurance and with higher education reported using a digital device such as a computer or tablet compared to responders with public medical insurance and less than 16 years of education (p&lt;0.001, p&lt;0.001, respectively). Additionally, a significantly larger percentage of caretakers with higher education reported using a smartphone when compared to caretakers with less than 16 years of education (p=0.006). Conclusions: Both level of education and insurance status correlate with the utilization of informative resources and digital devices by families seeking to learn more about complex cardiac conditions in children.
Abstract 9570: Different Distribution of CD163 Positive Macrophages in Thrombus Retrieved From Infarct-Related Artery: Atherothrombosis vs. Cardiogenic Thrombosis, Pathological Analyses From the MITO Study
Authors: Tomomi Koizumi, Noriyuki Kato, Yukinori Inadome, Koji Nakano, Yuu Yamada, Yuto Abe, Fumimasa Tabata, Tomosato Yamazaki, Masao Ono
Journal: Circulation (2022)

Introduction: Diagnosis of cardiogenic thrombosis is important because anticoagulant therapy is recommended for its secondary prevention. However, it is difficult to make a clear distinction in the pathogenesis between atherothrombosis and cardiogenic thrombosis. Hypothesis: Role of macrophage in thrombus formation is different between atherothrombosis and cardiogenic thrombosis. Methods: The Macrophage in Thrombus (MITO) study is a prospective observational study examining pathological and biological differences of arterial thrombus between atherothrombosis and cardiogenic thrombosis. Patients with ST elevation myocardial infarction (STEMI) or acute ischemic stroke (AIS) whose solid thrombus could be retrieved from the infarct-related artery were enrolled. Patients were divided into 2 groups as follows; STEMI with sinus rhythm: Group A (presumed atherothombosis) and AIS with atrial fibrillation (presumed cardiogenic thrombosis): Group C, and compared macrophage score as follows; 1:almost no macrophages detected byх40; 2:difficult to detect the macrophages in х20 but detected by х40; and 3:easy to detect macrophages in х20 in the thrombus. Serum levels of soluble CD163 were measured all the patients. Results: The score for CD163 positive macrophage of Group C (n=33) was significantly higher than that of Group A (n=32) (p&lt;0.01): Figure. Serum level of soluble CD163 in Group C (median 603 ng/ml, IQR 405, 788) tended to be higher than that in Group A (median 520 ng/ml, IQR: 314, 634); p=0.08. Conclusions: CD163 positive macrophages are more involved in the thrombus formation of cardiogenic thrombus than that of atherothrombosis. Detection of CD163 positive macrophages are likely to help discriminate between atherothrombosis thrombus versus cardiogenic thrombus.
Abstract 9501: Single-Cell Transcriptomic Analysis and Patient-Specific iPSCs Reveal Dysfunctional Coronary Arterial Endothelial Cells in Hypoplastic Left Heart Syndrome
Authors: Zhiyun Yu, Xin Zhou, Ziyi Liu, Victor PastranaGomez, Yu Liu, Minzhe Guo, Lei Tian, Timothy J Nelson, Nian Wang, Seema Mital, David Chitayat, Joseph C Wu, Marlene Rabinovitch, Sean M Wu, Michael Snyder, Yifei Miao, Mingxia Gu
Journal: Circulation (2022)

Introduction: Hypoplastic left heart syndrome (HLHS) is a severe form of single ventricle congenital heart disease characterized by the underdeveloped left ventricle. Early serial postmortem examinations revealed a high rate of coronary artery abnormalities in HLHS fetal hearts (e.g., thickened wall and kinking arteries). However, the intrinsic defect in HLHS coronary vessels and its genetic basis remain unclear. Methods: We profiled human fetal heart with an underdeveloped left ventricle (ULV) and induced pluripotent stem cells derived endothelial cells (iPSC-ECs) from HLHS patients at single-cell resolution. CD144 + / NPR3 - vascular ECs were selected and classified as venous, arterial, and late arterial populations. To study the arterial EC phenotypes, we generated iPSC-arterial ECs (AECs, CDH5 + CXCR4 + NT5E -/low ) derived from 3 HLHS patients and 3 age-matched controls, and evaluated their functionalities including cell cycle regulation, angiogenesis, and inflammatory response. Results: Revealed by single cell RNA-seq and subsequent gene ontology analysis, ULV late arterial EC population showed significant defects in EC development, proliferation, angiogenesis, and Notch signaling compared to the control. Consistently, HLHS iPSCs exhibited impaired AEC differentiation judged by the reduced CXCR4 + NT5E -/low AEC progenitors. Mature HLHS iPSC-AECs showed reduced angiogenesis and enhanced G0/G1 cell cycle arrest with downregulated cell cycle-related genes (e.g., Ki67, CCND1/2 ). Healthy human aortic smooth muscle cells exhibited abnormal proliferation and synthetic phenotypes when co-cultured with HLHS iPSC-AECs. Additionally, NOTCH pathway genes (e.g., DLL4, HEY1, GJA5 ) were suppressed in both ULV AECs and HLHS iPSC-AECs. HLHS de novo variant KMT2D directly regulated the transcription of NOTCH targeted genes involved in arterial development and proliferation via H3K4me2. Intriguingly, the treatment of NOTCH ligands (Jag1, Dll1) significantly improved the proliferation of HLHS AECs. Conclusions: Our study revealed that HLHS coronary AECs were dysfunctional in angiogenesis, proliferation, and EC-SMC interaction. KMT2D-NOTCH signaling may contribute to the impaired development and proliferation of HLHS AECs.